Carbidopa/Levodopa Combined With Behavioral Therapy for the Treatment of Cocaine Dependence

Contingency Management Plus Levodopa/Carbidopa for Treatment of Cocaine Dependence

Cocaine dependence is a major public health problem and the development of a treatment for this disorder is a priority. To date, treatment interventions based on positive incentive principles have shown the strongest effects for improving substance use outcomes. One such example is contingency management (CM) interventions in which nondrug rewards are used to compete with cocaine. Recent evidence suggests that certain medications improve response to CM interventions, particularly agents that target dopamine reward systems in the brain. A promising dopamine-enhancing medication is levodopa. The study team has observed the strongest effects of levodopa when the medication is administered in the context of CM therapy, perhaps through mechanisms that enhance reward saliency. The proposed study is designed to further evaluate this promising treatment approach. Cocaine dependent outpatients will participate in a randomized, 2-group (levodopa vs. placebo), double-blind clinical trial. CM will be behavioral therapy platform for both treatment groups. The study will test the primary hypothesis that CM+levodopa will be more effective than CM+placebo in reducing cocaine use. This study is expected to validate the usefulness of a new behavioral-pharmacological treatment approach for cocaine dependence.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Placebo; Drug: levodopa; Behavioral: Cognitive Behavioral Therapy; Behavioral: Contingency Management

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• between 18 and 60 years of age
• meet Diagnostic and Statistical Manual of Mental Disorders, 4th. Edition (DSM-IV) criteria for current cocaine dependence.
• be in acceptable health on the basis of interview, medical history and physical exam.

Exclusion Criteria:

• current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, or nicotine.
• have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe.
• have significant current suicidal or homicidal ideation.
• have medical conditions contraindicating levodopa/carbidopa pharmacotherapy. Conditions include severe pulmonary disease (bronchial asthma, emphysema), cardiovascular disease (severe or history of myocardial infarction with residual arrhythmias), narrow angle glaucoma, melanoma, history of peptic ulcer, renal function impairment.
• taking medications known to have significant drug interactions with levodopa/carbidopa (e.g., monoamine oxidase (MAO) inhibitors, anticonvulsants, haloperidol, phenothiazines, selegiline, anesthetics).
• currently or recently (last 3 months) treated for substance use or another psychiatric condition.
• having conditions of probation or parole requiring reports of drug use to officers of the court.
• impending incarceration.
• pregnant or nursing for female patients.
• inability to read, write, or speak English.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levodopa pharmacotherapy; Levodopa pharmacotherapy (800mg levodopa and 200mg carbidopa per day), cognitive behavioral therapy (CBT), and contingency management (CM).	Drug: levodopa; 800mg levodopa and 200mg carbidopa per day; Other Names: Sinemet; Behavioral: Cognitive Behavioral Therapy; Participants received individual cognitive behavioral therapy (CBT) in 50-minute weekly sessions. These sessions were manual-driven and based on the relapse prevention model proposed by Marlatt and Gordon (1985). Trained masters-level therapists, under the supervision of senior therapists and the principal investigator, worked with participants to teach them how to recognize and cope with risky situations that could influence their cocaine use through self-monitoring of situational craving and drug use stimuli, coping skills training, and lifestyle modifications.; Behavioral: Contingency Management; An abstinence-based contingency management (CM) procedure was used. Participants earned vouchers according to the reward schedule recommended by Budney and Higgins (1998), beginning at $2.50 for the first cocaine-negative urine. For each consecutive cocaine-negative urine, voucher values increased by $1.25 with a $10 bonus given for provision of three consecutive cocaine-negative urines within a week. A cocaine-positive urine or failure to provide a scheduled urine sample resulted in a reset of the schedule to the initial value of $2.50. After provision of five negative urines, the voucher returned to the value prior to the reset. Participants were able to redeem their vouchers for small amounts of cash (≤$25) or gift cards for goods and services.
Placebo Comparator: Placebo; Placebo, cognitive behavioral therapy (CBT), and contingency management (CM).	Drug: Placebo; Placebo; Behavioral: Cognitive Behavioral Therapy; Participants received individual cognitive behavioral therapy (CBT) in 50-minute weekly sessions. These sessions were manual-driven and based on the relapse prevention model proposed by Marlatt and Gordon (1985). Trained masters-level therapists, under the supervision of senior therapists and the principal investigator, worked with participants to teach them how to recognize and cope with risky situations that could influence their cocaine use through self-monitoring of situational craving and drug use stimuli, coping skills training, and lifestyle modifications.; Behavioral: Contingency Management; An abstinence-based contingency management (CM) procedure was used. Participants earned vouchers according to the reward schedule recommended by Budney and Higgins (1998), beginning at $2.50 for the first cocaine-negative urine. For each consecutive cocaine-negative urine, voucher values increased by $1.25 with a $10 bonus given for provision of three consecutive cocaine-negative urines within a week. A cocaine-positive urine or failure to provide a scheduled urine sample resulted in a reset of the schedule to the initial value of $2.50. After provision of five negative urines, the voucher returned to the value prior to the reset. Participants were able to redeem their vouchers for small amounts of cash (≤$25) or gift cards for goods and services.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Abstinence From Cocaine as Assessed by Treatment Effectiveness Score (TES)	The Treatment Effectiveness Score (TES) is the number of cocaine-negative urines collected out of the total scheduled urine tests for the 12-week trial (36 total scheduled urine tests per participant). The mean number of cocaine-negative urines over all time points is reported in this outcome measure.	12 weeks of treatment

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Joy M Schmitz, PhD, University of Texas at Houston

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 9, 2008
• First Submitted That Met QC Criteria: July 9, 2008
• First Posted (Estimate): July 11, 2008

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: March 23, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Cocaine, levodopa, contingency management
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: 1R01DA023608-01 (U.S. NIH Grant/Contract); DPMCDA (Other Identifier: NIDA); R01DA023608-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No